ASSOCIATION OF ALCOHOLISM WITH THE N-GLYCOSYLATION POLYMORPHISM OF PSEUDODEFICIENT HUMAN ARYLSULFATASE-A

The IIIa and IIIb electrophoretic variants of arylsulfatase A (EC 3.1. 6.8) are 12 times more prevalent in alcoholic than in nonalcoholic pop ulations. These variant enzymes, found in a subset of alcoholics, poss ess the pseudodeficient Asn(350)-Ser mutation of arylsulfatase A and, consequently, lack an N-linked glycan unit. These genetically determin ed variants of arylsulfatase A show reduced intracellular half-life, a nd cells from such individuals possess reduced enzymic activity. We pr opose that this polymorphism is an underlying genetic and biochemical factor contributing to the neuropathology and/or addiction pathway of this disease.